Centre for Nanoscience and Engineering, Indian Institute of Science, Bangalore, India.
Centre for Nanoscience and Engineering, Indian Institute of Science, Bangalore, India.
Micron. 2022 Nov;162:103347. doi: 10.1016/j.micron.2022.103347. Epub 2022 Sep 1.
Nanopore-based techniques are widely used owing to their diverse applications such as DNA sequencing, ion detection, gas filtration, protein sequencing, and numerous other applications. Although commercialized sequencing methods are based on biological nanopores, solid-state nanopore technology is emerging due to its several advantages over biological nanopores, such as its tunable size, chemical and mechanical stability, and possibilities for easy integration with measurement electronics. The unavailability of rapid, low-cost, easy solid-state nanopore fabrication methods with industrial scalability is one of the current bottlenecks in this domain. Among all nanopore fabrication techniques, the Transmission electron microscope (TEM) based fabrication method is frequently used in research labs due to its capability of drilling and tuning nanopores with high accuracy. Given that there are no other methods capable of imaging and fabricating nanopores simultaneously, it is important to discuss the related methods and protocols of TEM. This review focuses on the various aspects of nanopore technology using TEM, from pore fabrication to imaging. Hybrid nanopores are also emerging, which combine the benefits of biological and solid-state nanopores. These can be formed by integrating DNA origami with solid-state nanopores. Creating and imaging DNA origami structures also presents several challenges. We also review DNA origami imaging using conventional TEM. We hope that this review will provide a one-stop reference to TEM applications on solid-state nanopores from fabrication to bioimaging and boost further research in this area.
基于纳米孔的技术由于其广泛的应用而被广泛使用，例如 DNA 测序、离子检测、气体过滤、蛋白质测序以及许多其他应用。尽管商业化的测序方法基于生物纳米孔，但由于其相对于生物纳米孔的几个优势，如可调节的尺寸、化学和机械稳定性以及与测量电子设备易于集成的可能性，固态纳米孔技术正在兴起。缺乏具有工业可扩展性的快速、低成本、易于制造的固态纳米孔的方法是该领域当前的瓶颈之一。在所有纳米孔制造技术中，基于透射电子显微镜（TEM）的制造方法由于其能够高精度地钻孔和调谐纳米孔而在研究实验室中经常使用。由于没有其他能够同时成像和制造纳米孔的方法，因此讨论 TEM 的相关方法和协议非常重要。本综述重点介绍了 TEM 在从孔制造到成像的各个方面的纳米孔技术。混合纳米孔也在兴起，它结合了生物和固态纳米孔的优势。这些可以通过将 DNA 折纸与固态纳米孔集成来形成。创建和成像 DNA 折纸结构也带来了一些挑战。我们还回顾了使用传统 TEM 对 DNA 折纸结构的成像。我们希望本综述将为从制造到生物成像的固态纳米孔的 TEM 应用提供一站式参考，并推动该领域的进一步研究。
